An attenuated vaccine is a vaccine created by reducing the virulence of a pathogen, but still keeping it viable (or "live").[1] Attenuation takes an infectious agent and alters it so that it becomes harmless or less virulent. These vaccines contrast to those produced by "killing" the virus (inactivated vaccine). Attenuated vaccines represent one type of vaccine that have been developed, others are presented in this diagram. Three examples of live, attenuated vaccines are the rabies vaccine, initiated in the late 1890s by Louis Pasteur and Émile Roux,polio vaccine developed by Albert Sabin in the 1960s, and the measles vaccine developed by John Franklin Enders in 1963.
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Because these vaccines are so similar to the natural infection that they help prevent, they create a strong and long-lasting immune response. Just 1 or 2 doses of most live vaccines can give an individual a lifetime of protection against a germ and the disease it causes.
Examples
editHistory
editThe first live attenuated vaccine was developed by Louis Pasteur (1822–1895), through his research concerning chicken cholera, anthrax and rabies. Initially, Pasteur intentionally infected chickens by feeding them cholera-contaminated feed so that he could observe how the pathology progressed. Through an assistant's accident, month old bacterial cultures were used instead of fresh cultures for one of the experiments, with complete fatality of chickens being replaced with mild symptoms of infection. When Pasteur later re-injected the chickens with fresh, infectious bacteria, they did not fall ill or show any symptoms of infection.[2, 3] Pasteur developed a live attenuated anthrax vaccine in his laboratory, containing bacterial cultures treated with carbolic acid. He was able to show that vaccinated animals survived subsequent infection by anthrax while the unvaccinated group used as a control died.[4] Following this success, Pasteur in 1884 used an attenuated rabies vaccine obtained from desiccated brain tissue inactivated with formaldehyde, to provide immunity to dogs against rabies.[2] In 1885, Pasteur saved the life of a 9 year old boy who had been bitten by a rabid dog. The boy was first inoculated with the mildest version of of the virus, the most attenuated version of the virus, then with more severe, less attenuated virus each day for 10 days.[3, 5] The first live polio vaccine was first tried out by Hilary Kaprowski in 1950. [6] This prototype was improved upon by Albert Sabin and administered to the public in the 1960's [7]. Even today eradication of polio is incomplete, pockets of polio cases continue in several countries. [8] A live, attenuated measles vaccine was developed and administered in the 1960's. [9] Regardless of its enormous worldwide distribution and success, administration of the measles vaccine in children has frequently become a focal point for dispute by the anti-vaccination movement. [10]
Developments since 1960
editWell established, safe, and immunogenic attenuated vaccines can be used as scaffolds to carry portions of other infectious diseases that are too dangerous to be developed as attenuated vaccines on their own. For example, antigens from human immunodeficiency virus have been inserted into the live attenuated measles or rubella vaccine strain RA27/3. In this way, with a single innoculation, rubella can be used as a safe vector to vaccinate against other infectious diseases in addition to German measles.[11]
References
edit- ^ Badgett MR, Auer A, Carmichael LE, Parrish CR, Bull JJ (October 2002). "Evolutionary dynamics of viral attenuation". J. Virol. 76 (20): 10524–9. doi:10.1128/JVI.76.20.10524-10529.2002. PMC 136581. PMID 12239331.
3. Bazin H. History of Vaccine Development. (Pasteur and the Birth of Vaccines Made in the Laboratory Chapter). New York, NY: Springer Science & Business Media; (2011). p. 33–45. [Google Scholar]
4. Sternbach G. The history of anthrax. J Emerg Med (2003) 24(4):463–7.10.1016/S0736-4679(03)00079-9 [PubMed] [CrossRef] [Google Scholar]
5. Bourhy H, Perrot A, Cavaillon J. Vaccines: A Biography (Rabies). New York, NY: Springer Science & Business Media; (2010). p. 73–85. [Google Scholar]
6. Koprowski, Hilary (15 October 2010). "Interview with Hilary Koprowski, sourced at History of Vaccines website". College of Physicians of Philadelphia. Archived from the original on 15 May 2016. Retrieved 15 October 2010.
7. Sabin AB, Boulger LR (1973). "History of Sabin attenuated poliovirus oral live vaccine strains". Journal of Biological Standardization. 1 (2): 115–18. doi:10.1016/0092-1157(73)90048-6.
8. Losey L, Ogden E, Bisrat F, Solomon R, Newberry D, Coates E, Ward D, Hilmi L, LeBan K, Burrowes V, Perry HB. The CORE Group Polio Project: An Overview of Its History and Its Contributions to the Global Polio Eradication Initiative. Am J Trop Med Hyg. 2019 Oct;101(4_Suppl):4-14. doi: 10.4269/ajtmh.18-0916.
9. Measles History". U.S. Centers for Disease Control and Prevention (CDC). 5 February 2018. Retrieved 28 January 2020.
10. Measles, Mumps, Rubella Vaccination and Autism: A Nationwide Cohort Study. Hviid A, Hansen JV, Frisch M, Melbye M.Ann Intern Med. 2019 Apr 16;170(8):513-520. doi: 10.7326/M18-2101. Epub 2019 Mar 5.PMID: 30831578
11. Development of replication-competent viral vectors for HIV vaccine delivery. Parks CL, Picker LJ, King CR.Curr Opin HIV AIDS. 2013 Sep;8(5):402-11. doi: 10.1097/COH.0b013e328363d389.PMID: 23925000